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Open data
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Basic information
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| Title | Structure of C5a-pep bound human C5aR1 in complex with Go | ||||||||||||
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Keywords | GPCR / G protein / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
| Function / homology | Function and homology informationpresynapse organization / complement component C5a signaling pathway / complement component C5a receptor activity / response to peptidoglycan / Muscarinic acetylcholine receptors / G protein-coupled acetylcholine receptor activity / sensory perception of chemical stimulus / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding ...presynapse organization / complement component C5a signaling pathway / complement component C5a receptor activity / response to peptidoglycan / Muscarinic acetylcholine receptors / G protein-coupled acetylcholine receptor activity / sensory perception of chemical stimulus / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / complement receptor mediated signaling pathway / vesicle docking involved in exocytosis / G protein-coupled dopamine receptor signaling pathway / positive regulation of neutrophil chemotaxis / regulation of locomotion / regulation of heart contraction / positive regulation of macrophage chemotaxis / parallel fiber to Purkinje cell synapse / amyloid-beta clearance / positive regulation of vascular endothelial growth factor production / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / cellular defense response / postsynaptic modulation of chemical synaptic transmission / neutrophil chemotaxis / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / astrocyte activation / muscle contraction / secretory granule membrane / Regulation of Complement cascade / Peptide ligand-binding receptors / positive regulation of epithelial cell proliferation / locomotory behavior / microglial cell activation / negative regulation of insulin secretion / G protein-coupled receptor activity / mRNA transcription by RNA polymerase II / GABA-ergic synapse / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / cognition / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / apical part of cell / chemotaxis / Activation of the phototransduction cascade / positive regulation of angiogenesis / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / sensory perception of taste / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / positive regulation of cytosolic calcium ion concentration / retina development in camera-type eye / cell body / G protein activity / GTPase binding / presynaptic membrane / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / basolateral plasma membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / chemical synaptic transmission / Ras protein signal transduction Similarity search - Function | ||||||||||||
| Biological species | Homo sapiens (human) / ![]() | ||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.15 Å | ||||||||||||
Authors | Banerjee R / Yadav MK / Ganguly M / Mishra S / Dalal A / Shukla AK / Gati C | ||||||||||||
| Funding support | India, United Kingdom, 3 items
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Citation | Journal: bioRxiv / Year: 2025Title: Molecular fingerprints of a convergent mechanism orchestrating diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptors. Authors: Sudha Mishra / Manish K Yadav / Annu Dalal / Manisankar Ganguly / Ravi Yadav / Kazuhiro Sawada / Divyanshu Tiwari / Nabarun Roy / Nilanjana Banerjee / Jenny N Fung / Jianina Marallag / ...Authors: Sudha Mishra / Manish K Yadav / Annu Dalal / Manisankar Ganguly / Ravi Yadav / Kazuhiro Sawada / Divyanshu Tiwari / Nabarun Roy / Nilanjana Banerjee / Jenny N Fung / Jianina Marallag / Cedric S Cui / Xaria X Li / John D Lee / Calvin Aaron Dsouza / Shirsha Saha / Parishmita Sarma / Ganita Rawat / Houming Zhu / Htet A Khant / Richard J Clark / Fumiya K Sano / Ramanuj Banerjee / Trent M Woodruff / Osamu Nureki / Cornelius Gati / Arun K Shukla / ![]() Abstract: Complement anaphylatoxin receptors (C3aR and C5aR1) are prototypical G protein-coupled receptors (GPCRs) playing crucial physiological roles in innate immunity by combating pathogenic infections and ...Complement anaphylatoxin receptors (C3aR and C5aR1) are prototypical G protein-coupled receptors (GPCRs) playing crucial physiological roles in innate immunity by combating pathogenic infections and orchestrating inflammatory responses. They continue to be important therapeutic targets for multiple disorders including autoimmune diseases, acute and chronic inflammation, and allergy-related conditions. Recent structural coverage has provided important insights into their activation and signaling, however, confounding observations in the literature related to ligand efficacy and functional responses, especially in different model systems, present a major challenge for drug discovery efforts. Here, we systematically and comprehensively profile a broad set of natural and synthetic ligands at C3aR and C5aR1 and discover a previously unanticipated level of functional specialization in terms of species-specific pharmacology and receptor activation. Taking a lead from this, we determine seventeen cryo-EM structures of different ligand-receptor-G-protein complexes and uncover distinct orientation of agonists between the human and mouse receptors despite an overlapping positioning in the orthosteric binding pocket. Combined with extensive mutagenesis and functional assays, these structural snapshots allow us to decode and validate a convergent molecular mechanism involving a "Five-Point-Switch" in these receptors that orchestrates the recognition and efficacy of diverse agonists. We also identify species-specific differences at the level of phosphorylation patterns encoded in the carboxyl-terminus of these receptors and directly visualize their impact on βarr binding and activation using cryo-EM structures. Interestingly, we observe that βarrs engage with the mouse C5aR1 using a variation of previously discovered P-X-P-P phosphorylation motif via a "Sliding-Mechanism" and also exhibit distinct oligomeric state for the human vs. mouse receptors. Taken together, this study elucidates functional specialization at the complement anaphylatoxin receptors and underlying molecular mechanisms, offering a previously lacking framework with direct and immediate implications for the development of novel therapeutics. | ||||||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_64291.map.gz | 57.4 MB | EMDB map data format | |
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| Header (meta data) | emd-64291-v30.xml emd-64291.xml | 26.8 KB 26.8 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_64291_fsc.xml | 8.4 KB | Display | FSC data file |
| Images | emd_64291.png | 91.4 KB | ||
| Filedesc metadata | emd-64291.cif.gz | 7.4 KB | ||
| Others | emd_64291_half_map_1.map.gz emd_64291_half_map_2.map.gz | 59.5 MB 59.5 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-64291 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-64291 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9umrMC ![]() 9kugC ![]() 9kutC ![]() 9kv6C ![]() 9kv8C ![]() 9kvpC ![]() 9kwgC ![]() 9kwxC ![]() 9kx6C ![]() 9kxsC ![]() 9ky2C ![]() 9kyuC ![]() 9kz2C ![]() 9kz8C ![]() 9kzkC ![]() 9l0hC ![]() 9umjC ![]() 9umxC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_64291.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.2094 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #2
| File | emd_64291_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #1
| File | emd_64291_half_map_2.map | ||||||||||||
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Sample components
+Entire : C5a-pep cound to human C5aR1 in complex with Go
+Supramolecule #1: C5a-pep cound to human C5aR1 in complex with Go
+Supramolecule #2: human C5a anaphylatoxin chemotactic receptor 1
+Supramolecule #3: Guanine nucleotide-binding protein G(o) subunit alpha
+Supramolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Supramolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Supramolecule #6: Antibody fragment - ScFv16
+Supramolecule #7: C5a-pep ligand
+Macromolecule #1: Muscarinic acetylcholine receptor M4,C5a anaphylatoxin chemotacti...
+Macromolecule #2: Guanine nucleotide-binding protein G(o) subunit alpha
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #5: Antibody fragment - ScFv16
+Macromolecule #6: C5a-pep ligand
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: COUNTING / Average electron dose: 55.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
| Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
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| Output model | ![]() PDB-9umr: |
Movie
Controller
About Yorodumi




Keywords
Homo sapiens (human)
Authors
India,
United Kingdom, 3 items
Citation




























































Z (Sec.)
Y (Row.)
X (Col.)






































FIELD EMISSION GUN


